Ambient Air Pollution Increases the Risk of Cerebrovascular and Neuropsychiatric Disorders through Induction of Inflammation and Oxidative Stress

Abstract

Exposure to ambient air pollution is a well-established determinant of health and disease. The Lancet Commission on pollution and health concludes that air pollution is the leading environmental cause of global disease and premature death. Indeed, there is a growing body of evidence that links air pollution not only to adverse cardiorespiratory effects but also to increased risk of cerebrovascular and neuropsychiatric disorders. Despite being a relatively new area of investigation, overall, there is mounting recent evidence showing that exposure to multiple air pollutants, in particular to fine particles, may affect the central nervous system (CNS) and brain health, thereby contributing to increased risk of stroke, dementia, Parkinson's disease, cognitive dysfunction, neurodevelopmental disorders, depression and other related conditions. The underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests inflammation and oxidative stress to be crucial factors in the pathogenesis of air pollution-induced disorders, driven by the enhanced production of proinflammatory mediators and reactive oxygen species in response to exposure to various air pollutants. From a public health perspective, mitigation measures are urgent to reduce the burden of disease and premature mortality from ambient air pollution.

Keywords: air pollution; cerebrovascular disorders; dementia; inflammation; mental disorders; neurological disorders; oxidative stress; particulate matter; stroke.

Figure 1

Global risk factors for global deaths in 1990 compared with 2015 outlined in the Global Burden of Disease Study (GDB). Reused from Münzel et al. [10] with permission. Copyright © 2020, Oxford University Press.

Figure 2

There are four main types of air pollution sources including natural, area, stationary, and mobile sources producing PM0.1, PM2.5, PM10, reactive gases including volatile organic compounds (VOCs). Primary pollutants (the indicated gases and solid particles) may undergo further toxification in the environment, e.g., by photochemical reactions by UV light producing more reactive gases or more toxic carbohydrate products on the particle surface (termed particle “aging”) [12] as well as loading of the particles with heavy/transition metals and bacterial/fungal endotoxins, leading to secondary biological toxicity [15,16,17]. The majority of coarse particles come from sediments (desert sand) and pollen from plants. Modified from Münzel et al. [18] with permission. Copyright 2020, Mary Ann Liebert, Inc., publishers. Open access source for sandstorm and plant pollen images can be found at Pixabay (https://pixabay.com/de/).

Figure 3

Summary of pathophysiological mechanisms by which air pollutants cause increased oxidative stress, and inflammation, thereby contributing to cerebrovascular, neurological, mental, and cardiorespiratory disorders. (A) Uptake and cardiorespiratory health effects triggered by air pollution constituents. (B) Key events that contribute to neurological and mental by air pollution constituents. Ambient PM particles are often loaded with environmental toxins stemming from particle “aging” by UV-induced photoreactions or modifications upon interaction with reactive gases in the atmosphere [12]. In addition, loading of the particles with environmental endotoxins and heavy metals enhances their direct biochemical reactivity [15,16,17]. Summarized from Münzel et al. [10] (A) and Daiber et al. [38] (B) with permission. Copyright © 2020, Oxford University Press (A) and © 2020 International Union of Biochemistry and Molecular Biology (B). SNS, sympathetic nervous system; UF, ultrafine.

Figure 4

Population attributable risk of cerebrovascular disease associated with air pollution worldwide. Estimates from Institute for Health Metrics and Evaluation (IHME). Reused from Lee et al. [55] with permission according to the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).

Figure 5

Proposed concept how air pollution constituents contribute to neurological and mental disorders. Uptake of fine particulate matter, reactive gases or secondary environmental toxins (bound to the solid or liquid aerosol particles) such as heavy metals, endotoxins or photoreaction/atmospheric chemistry products (e.g., reactive aldehydes, nitrated VOCs) by three major pathways (indirect or direct). Neuroinflammation and cerebral oxidative stress by microglia activation impairs vital pathways in the brain initiating pathophysiological processes such as amyloid deposition and neuron damage and loss. BBB, blood-brain barrier; iNOS, inducible nitric oxide synthase; TNFα, tumor necrosis factor alpha; IL-1β, interleukin 1beta; COX-2, (inducible) cyclooxygenase 2; NFκB, nuclear factor ‘kappa-light- chain-enhancer’ of activated B-cells; NOX-2, NADPH oxidase isoform 2 (phagocytic NADPH oxidase); oxLDL, oxidized low density lipoprotein; 4-HNE, 4-hydroxynonenal; 8-oxoG, 8-hydroxyguanosine; Aβ, amyloid beta peptide.